Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100ß, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS). METHODS: A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student's t-test was used to test for differences in CSF concentrations between patients of different AIS grades. RESULTS: The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either 'motor complete' (AIS A, B) or 'motor incomplete' (AIS C, D) (r=0.520, P<0.05). The mean S-100ß concentration in motor complete patients was significantly higher compared with motor incomplete patients; 377.2 µg l(-1) (s.d.±523 µg l(-1)) vs 57.1 µg l(-1) (s.d.±56 µg l(-1)) (P<0.05), respectively. Lastly, the mean NFH concentration in motor complete patients was significantly higher compared with motor incomplete patient, 11 813 ng l(-1) (s.d.±16 195 ng l(-1)) vs 1446.8 ng l(-1) (s.d.±1533 ng l(-1)), (P<0.05), respectively. CONCLUSION: In this study we identified differences in the structural CSF biomarkers NSE, S-100ß and NFH between motor complete and motor incomplete SCI patients. Our data showed no clear differences in any of the protein concentrations between the different AIS grades.

Design and rationale of a Prospective, Observational European Multicenter study on the efficacy of acute surgical decompression after traumatic Spinal Cord Injury: the SCI-POEM study.

OBJECTIVES: Despite many years of research, there is currently no treatment available that results in major neurological or functional recovery after traumatic spinal cord injury (tSCI). In particular, no conclusive data related to the role of the timing of decompressive surgery, and the impact of injury severity on its benefit, have been published to date. This paper presents a protocol that was designed to examine the hypothesized association between the timing of surgical decompression and the extent of neurological recovery in tSCI patients. STUDY DESIGN: The SCI-POEM study is a Prospective, Observational European Multicenter comparative cohort study. This study compares acute (<12 h) versus non-acute (>12 h, <2 weeks) decompressive surgery in patients with a traumatic spinal column injury and concomitant spinal cord injury. The sample size calculation was based on a representative European patient cohort of 492 tSCI patients. During a 4-year period, 300 patients will need to be enrolled from 10 trauma centers across Europe. The primary endpoint is lower-extremity motor score as assessed according to the 'International standards for neurological classification of SCI' at 12 months after injury. Secondary endpoints include motor, sensory, imaging and functional outcomes at 3, 6 and 12 months after injury. CONCLUSION: In order to minimize bias and reduce the impact of confounders, special attention is paid to key methodological principles in this study protocol. A significant difference in safety and/or efficacy endpoints will provide meaningful information to clinicians, as this would confirm the hypothesis that rapid referral to and treatment in specialized centers result in important improvements in tSCI patients.

Diffusion-weighted MR imaging within 24 h post-injury after traumatic spinal cord injury: a qualitative meta-analysis between T2-weighted imaging and diffusion-weighted MR imaging in 18 patients.

STUDY DESIGN: Only few studies have been published about diffusion-weighted imaging (DWI) within 24 h of traumatic spinal cord injury (tSCI). OBJECTIVES: The purpose of this study was to compare the imaging findings from conventional magnetic resonance imaging (MRI) and DWI in seven tSCI patients with findings in the existing literature. METHODS: Seven patients with tSCI at neurologic levels C2-T10 were examined with conventional MRI and DWI within 24 h post-injury. DWI was obtained with a b-factor of 1000 s mm(-2). American Spinal Injury Association (ASIA) scores and Spinal Cord Independence Measurement (SCIM) II item 12 after 12 months were collected. In addition, MEDLINE was searched from 1995 to 2010 to identify clinical tSCI studies reporting on MRI, DWI and apparent diffusion coefficient maps within 24 h post-injury to perform a meta-analysis. Images obtained with a b-factor of 1000 s mm(-2) were compared with lower b-factors. Differences were calculated using χ (2) tests. RESULTS: No associations were identified between the images of the seven tSCI patients and ASIA or SCIM II scores. Eighteen SCI patients (11 from the retrieved publications) were included in the meta-analysis. The detection rates of hyperintense signals on T2-weighted and DW imaging did not show significant differences at 94 and 72%, respectively. In addition, there were no significant differences in detection rates or diffusion abnormalities between subjects in whom DW images were obtained with a maximum b-factor of 1000 or <1000 s mm(-2). CONCLUSION: Our analysis suggests that T2-weighted and DW imaging have comparable detection rates for spinal cord damage in tSCI patients within 24 h post-injury.

Diagnostic criteria of traumatic central cord syndrome. Part 3: descriptive analyses of neurological and functional outcomes in a prospective cohort of traumatic motor incomplete tetraplegics.

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVES: To compare the neurological recovery and functional outcomes between traumatic central cord syndrome (TCCS) patients and motor incomplete tetraplegic patients. SETTING: European Multicenter Study of human spinal cord injury. METHODS: In 248 traumatic motor incomplete tetraplegics, initial phase (0-15 days) American Spinal Injury Association (ASIA) impairment grading, upper and lower extremity motor scores (UEMS and LEMS), upper and lower sensory scores and chronic phase (6 or 12 months) neurological outcomes were analyzed. In addition, chronic phase self-care and indoor mobility Spinal Cord Independence Measure (SCIM) items were studied. Tetraplegics were subdivided into three groups: (1) non-TCCS group (UEMSLEMS), (2) intermediate-TCCS group (UEMS=(1-9 points)

Is the outcome in acute spinal cord ischaemia different from that in traumatic spinal cord injury? A cross-sectional analysis of the neurological and functional outcome in a cohort of 93 paraplegics.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the neurological outcome between paraplegic patients with acute spinal cord ischaemia syndrome (ASCIS) or traumatic spinal cord injury (tSCI) and to investigate the influence of SCI aetiology on the total Spinal Cord Independence Measure (SCIM)-II score. SETTING: Level 1 trauma centre. METHODS: Initial (0-40 days) and chronic-phase (6-12 months) American Spinal Injury Association (ASIA) sensory scores, lower extremity motor score (LEMS) and chronic-phase total SCIM-II scores were analysed. Differences between ASCIS and tSCI patients were calculated using Student's t-tests and Wilcoxon signed-rank tests. To assess which variables give rise to the prediction of total SCIM-II score, a multiple linear regression analysis was used. These predictor variables included complete (ASIA impairment scale A) or incomplete SCI (AIS B, C, and D), aetiology, age and gender. RESULTS: Out of 93 included patients, 20 ASCIS and 73 tSCI patients were identified. In the complete SCI group, the initial pinprick scores were higher (P<0.05) in ASCIS patients compared with tSCI patients, 37.9 (95% Confidence Interval (CI), 23.3-52.5) and 27.3 (95% CI, 24.1-30.4), respectively. No other relevant differences in neurological outcome were identified between ASCIS and tSCI patients; however, the total SCIM-II scores were higher (P<0.05) in tSCI patients after 12 months. Using the linear regression analysis, we were able to predict 31.4% of the variability. The aetiology was not significant in this model. CONCLUSION: The neurological outcome was independent of the diagnosis ASCIS or tSCI. Furthermore, the diagnosis ASCIS or tSCI was not a significant predictor for total SCIM II scores after 12 months. SPONSORSHIP: This study was granted by the 'Internationale Stiftung für Forschung in Paraplegie' (IFP), Zürich, Switzerland.

Relevance of the diagnosis traumatic cervical Brown-Séquard-plus syndrome: an analysis based on the neurological and functional recovery in a prospective cohort of 148 patients.

STUDY DESIGN: Prospective multi-center cohort study. OBJECTIVES: To compare the neurological and functional recovery between tetraplegic Brown-Séquard-plus syndrome (BSPS) and incomplete tetraplegia (non-BSPS). SETTING: European Multicenter Study of Human Spinal Cord Injury (EM-SCI). METHODS: BSPS was defined as a traumatic incomplete spinal cord injury (SCI) with ipsilateral weakness and contralateral loss of pinprick sensation at neurologic levels C2-T1. Acute (0-15 days) and chronic phase (6 or 12 months) were assessed for the American Spinal Injury Association (ASIA) sensory scores, upper extremity motor scores and lower extremity motor scores. Furthermore, chronic phase scores of all Spinal Cord Independence Measure (SCIM) II items were analyzed. Differences in neurological and functional outcome between BSPS patients and non-BSPS patients were calculated using Student's t-tests and Wilcoxon signed rank tests. RESULTS: Out of 148 tetraplegic patients, 30 were diagnosed with BSPS. Patients with an ASIA impairment scale (AIS) B were significantly (P<0.001) more identified in non-BSPS patients (25%) compared with BSPS patients (3%), respectively. After 12 months, the median scores for sphincter management of the bladder for both BSPS and non-BSPS patients were 15. Both 25 and 75% quartile median scores were 15 for BSPS patients and 12 and 15 for non-BSPS patients (P<0.02). Except for the difference in bladder function, no significant differences were identified in other SCIM II subitems and ASIA motor or sensory scores between BSPS and non-BSPS patients when stratified for injury severity by excluding AIS B patients. CONCLUSION: Compared with incomplete tetraplegic patients, patients with cervical BSPS have a similar neurological and functional recovery when matched for the AIS.

Diagnostic criteria of traumatic central cord syndrome. Part 1: a systematic review of clinical descriptors and scores.

STUDY DESIGN: Systematic review. BACKGROUND: The applied definition of traumatic central cord syndrome (TCCS) lacks specific quantified diagnostic criteria. OBJECTIVE: To review currently applied TCCS diagnostic criteria and quantitative data regarding the 'disproportionate weakness' between the upper and lower extremities described in original studies reporting on TCCS subjects. METHODS: A MEDLINE (1966 to 2008) literature search was conducted. The descriptors applied to define TCCS were extracted from all included articles. We included original studies that reported on the differences in motor score (based on the Medical Research Council scale) between the total upper extremity motor score (UEMS) and the total lower extremity motor score (LEMS), in a minimum of five TCCS patients at the time of hospital admission. The mean difference between the total UEMS and the total LEMS of the patients included in each study was calculated. Case reports were excluded. RESULTS: None of the identified studies on TCCS patients reported inclusion and/or exclusion criteria using a quantified difference between the UEMS and LEMS. Out of 30 retrieved studies, we identified seven different clinical descriptors that have been applied as TCCS diagnostic criteria. Nine studies reporting on a total of 312 TCCS patients were eligible for analysis. The mean total UEMS was 10.5 motor points lower than the mean total LEMS. CONCLUSIONS: There is no consensus on the diagnostic criteria for TCCS. Nevertheless, this review revealed an average of 10 motor points between the UEMS and LEMS as a possible TCCS diagnostic criterion. However, further discussion by an expert panel will be required to establish definitive diagnostic criteria.

Diagnostic criteria of traumatic central cord syndrome. Part 2: a questionnaire survey among spine specialists.

STUDY DESIGN: A questionnaire survey. OBJECTIVES: To evaluate the need for the introduction of quantitative diagnostic criteria for the traumatic central cord syndrome (TCCS). SETTING: An online questionnaire survey with participants from all over the world. METHODS: An invitation to participate in an eight-item online survey questionnaire was sent to surgeon members of AOSpine International. RESULTS: Out of 3340 invited professionals, 157 surgeons (5%) from 41 countries completed the survey. Whereas most of the respondents (75%) described greater impairment of the upper extremities than of the lower extremities in their own TCCS definitions, symptoms such as sensory deficit (39%) and bladder dysfunctions (24%) were reported less frequently. Initially, any difference in motor strength between the upper and lower extremities was considered most frequently (23%) as a 'disproportionate' difference in power. However, after presenting literature review findings, the majority of surgeons (61%) considered a proposed difference of at least 10 points of power (based on the Medical Research Council scale) in favor of the lower extremities as an acceptable cutoff criterion for a diagnosis of TCCS. Most of the participants (40%) felt that applying a single criterion to the diagnosis of TCCS is insufficient for research purposes. CONCLUSION: Various definitions of TCCS were used by physicians involved in the spinal trauma care. The authors consider a difference of at least 10 motor score points between upper and lower extremity power a clear diagnostic criterion. For clinical research purposes, this diagnostic criterion can be considered as a face valid addendum to the commonly applied TCCS definition as introduced by Schneider et al.

ASIA impairment scale conversion in traumatic SCI: is it related with the ability to walk? A descriptive comparison with functional ambulation outcome measures in 273 patients.

STUDY DESIGN: Prospective multicenter longitudinal cohort study. OBJECTIVES: To determine the relationship between improvements of the American Spinal Injury Association/International Spinal Cord Society (ASIA/ISCoS) neurological standard scale (AIS) outcome measure and improvements of functional ambulatory outcome measures in patients with traumatic spinal cord injury (SCI). SETTING: European multicenter study of human SCI (EM-SCI). METHODS: In 273 eligible patients with traumatic SCI, acute (0-15 days) and chronic phase (6 or 12 months) AIS grades, timed up and go (TUG) test and 10-m walk test (10MWT) outcome measurements were analyzed. Subanalysis of those patients who did have AIS conversion was performed to assess its relation with functional ambulatory outcomes. RESULTS: Studied population consisted of 161 acute phase AIS grade A patients; 37 grade B; 43 grade C and 32 acute phase AIS grade D patients. Forty-two patients (26%) converted from AIS grade A, 27 (73%) from grade B, 32 (75%) from grade C and five patients (16%) from AIS grade D. The frequencies of AIS conversions and functional ambulation recovery outcomes were significantly different (P<0.001) in patients with motor complete SCI. The ratio of patients with both recovery of ambulatory function and AIS conversion (n=101) differed significantly (P<0.001) between the acute phase AIS grade scores; AIS grade A (6/40 patients, 15%), B (9/27 patients, 33%), C (23/29 patients, 79%) and D (5/5 patients 100%). CONCLUSIONS: The AIS conversion outcome measure is poorly related to the ability to walk in traumatic SCI patients. Therefore, the authors recommend the use of functional ambulation recovery outcome measures in prognosticating the recovery of walking capacity and performance of patients with SCI.

Is determination between complete and incomplete traumatic spinal cord injury clinically relevant? Validation of the ASIA sacral sparing criteria in a prospective cohort of 432 patients.

STUDY DESIGN: Prospective multicenter longitudinal cohort study. OBJECTIVE: To validate the prognostic value of the acute phase sacral sparing measurements with regard to chronic phase-independent ambulation in patients with traumatic spinal cord injury (SCI). SETTING: European Multicenter Study of Human Spinal Cord Injury (EM-SCI). METHODS: In 432 patients, acute phase (0-15 days) American Spinal Injury Association (ASIA)/International Spinal Cord Society neurological standard scale (AIS) grades, ASIA sacral sparing measurements, which are S4-5 light touch (LT), S4-5 pin prick (PP), anal sensation and voluntary anal contraction; and chronic phase (6 or 12 months) indoor mobility Spinal Cord Independence Measure (SCIM) measurements were analyzed. Calculations of positive and negative predictive values (PPV/NPV) as well as univariate and multivariate logistic regressions were performed in all four sacral sparing criteria. The area under the receiver-operating characteristic curve (AUC) ratios of all regression equations was calculated. RESULTS: To achieve independent ambulation 1-year post injury, a normal S4-5 PP score showed the best PPV (96.5%, P<0.001, 95% confidence interval (95% CI): 87.9-99.6). Best NPV was reported in the S4-5 LT score (91.7%, P<0.001, 95% CI: 81.6-97.2). The use of the combination of only voluntary anal contraction and the S4-5 LT and PP sensory scores (AUC: 0.906, P<0.001, 95% CI: 0.871-0.941) showed significantly better (P<0.001, 95% CI: 0.038-0.128) discriminating results in prognosticating 1-year independent ambulation than with the use of currently used distinction between complete and incomplete SCI (AUC: 0.823, P<0.001, 95% CI: 0.781-0.864). CONCLUSIONS: Out of the four sacral sparing criteria, the acute phase anal sensory score measurements do not contribute significantly to the prognosis of independent ambulation. The combination of the acute phase voluntary anal contraction and the S4-5 LT and PP scores, predicts significantly better chronic phase-independent ambulation outcomes than the currently used distinction between complete and incomplete SCI. SPONSORSHIP: This study was granted by 'Acute Zorgregio Oost' and the 'Internationale Stiftung für Forschung in Paraplegie (IFP)'.

Biomarkers in spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: In traumatic spinal cord injury (SCI), much effort has been put into the evaluation of SCI severity and the prediction of recovery potential. An accurate prediction of the initial damage of the spinal cord that differentiates between the severities of SCI however, may help physicians in choosing a particular neuroprotective treatment in the acute phase. Neurochemical biomarkers may possibly fulfil these requirements. The aim of this review was to describe (1) the current status of neurochemical biomarkers in SCI; (2) their potential diagnostic role in SCI. METHODS: MEDLINE was searched from 1966 to 2008 to identify publications concerning biomarkers in traumatic SCI. RESULTS: The biomarkers S-100beta, neuron-specific enolase, neurofilament light chain, and Glial fibrillary acidic protein are significantly increased in cases of (experimental) spinal cord injury. Furthermore, increased serum concentrations of S-100beta have been correlated with an unfavourable functional outcome. Although biomarkers in SCI show promising results, considerations and shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor resuscitation, must be studied in greater detail before biomarkers can be utilised in the clinical care of SCI. CONCLUSIONS: Quantitative standards for determining the extent of SCI during the acute phase must be developed and validated. Even though increased concentrations of neurochemical biomarkers have been identified in patients with SCI, these do not yet provide a sensitive prognostic tool. Considering the limited availability of sensitive prognostic tools, neurochemical biomarkers of SCI should be evaluated and validated in future clinical trials.